Host Response to Sepsis

Work Group Host Response to Sepsis

Sepsis is a severe infection with organ failure resulting from an inappropriate and misdirected host immune response. On the one hand, the failure may be due to inefficient clearance of the infectious agent before it can damage the host's organs. On the other hand, an exaggerated or unbalanced inflammatory response may itself cause damage to the host organism.

In our department, we study the host response to severe infections in the broadest sense, with particular emphasis on understanding how and why an imbalanced systemic or tissue-local immune response compromises organ welfare and host health. In collaboration with numerous Jena and international collaborators, we use state-of-the-art optical, cell biological methods and functional screening platforms to delineate cellular signalling pathways that are dysregulated in the context of sepsis, both in the parenchyma and in immune cells. A particular focus of our laboratory is to elucidate the pathomechanisms of rare genetic paediatric neuropathies with features of neuroinflammation.

The PI and group leader Ignacio Rubio is also Head of the Section of Experimental Anaesthesiology at the UKJ Research Centre in Jena-Lobeda. He is a founding member and leader of a European consortium of immunologists and clinicians working on the immune response in sepsis (www.egis-online.eu).

Contact:

Apl. Prof. Dr. Ignacio Rubio
Dept. for Anesthesiology and Intensive Care Medicine
Jena University Hospital
Am Klinikum 1, D-07747 Jena (Germany)

Phone: +49 (0)3641 9325876
Fax: +49 (0)3641 9323362

Email:

Formation of Asc specks and concomitant recruitment of pro-caspase-1 during arming and assembly of the inflammasome in macrophages. ASC (red) and caspase-1 (green) protein decorated in THP-1 macrophages after priming with a TLR3 agonist and stimulation with nigericin to activate the canonical inflammasome. Recruitment of pro-caspase-1 to Asc-specks was severely impaired in CNPY3-deficient THP1 macrophages, indicating an essential role of the ER-resident chaperone CNPY3 in the assembly and activation of the inflammasome. See Ghait et al. Eur J Immunol 2022.

Selected Publications

Cajander S, Kox M, Scicluna BP, Weigand MA, Mora RA, Flohé SB, Martin-Loeches I, Lachmann G, Girardis M, Garcia-Salido A, Brunkhorst FM, Bauer M, Torres A, Cossarizza A, Monneret G, Cavaillon JM, Shankar-Hari M, Giamarellos-Bourboulis EJ, Winkler MS, Skirecki T, Osuchowski M, Rubio I, Bermejo-Martin JF, Schefold JC, Venet F (2023) Profiling the dysregulated immune response in sepsis: overcoming challenges to achieve the goal of precision medicine. Lancet Respir Med 10.1016/s2213-2600(23)00330-2 https://pubmed.ncbi.nlm.nih.gov/38142698/

Ghait M, Duduskar SN, Rooney M, Häfner N, Reng L, Göhrig B, Reuken PA, Bloos F, Bauer M, Sponholz C, Bruns T, Rubio I (2023) The non-canonical inflammasome activators Caspase-4 and Caspase-5 are differentially regulated during immunosuppression-associated organ damage. Front Immunol 14: 1239474 https://pubmed.ncbi.nlm.nih.gov/38106412/

Husain RA, Jiao X, Hennings JC, Giesecke J, Palsule G, Beck-Wödl S, Osmanović D, Bjørgo K, Mir A, Ilyas M, Abbasi SM, Efthymiou S, Dominik N, Maroofian R, Houlden H, Rankin J, Pagnamenta AT, Nashabat M, Altwaijri W, Alfadhel M, Umair M, Khouj E, Reardon W, El-Hattab AW, Mekki M, Houge G, Beetz C, Bauer P, Putoux A, Lesca G, Sanlaville D, Alkuraya FS, Taylor RW, Mentzel HJ, Hübner CA, Huppke P, Hart RP, Haack TB, Kiledjian M, Rubio I (2023) Biallelic NUDT2 variants defective in mRNA decapping cause a neurodevelopmental disease. Brain 10.1093/brain/awad434 https://pubmed.ncbi.nlm.nih.gov/38141063/

Kumari P, Vasudevan SO, Russo AJ, Wright SS, Fraile-Ágreda V, Krajewski D, Jellison ER, Rubio I, Bauer M, Shimoyama A, Fukase K, Zhang Y, Pachter JS, Vanaja SK, Rathinam VA (2023) Host extracellular vesicles confer cytosolic access to systemic LPS licensing non-canonical inflammasome sensing and pyroptosis. Nat Cell Biol 25: 1860-1872 https://pubmed.ncbi.nlm.nih.gov/37973841/

Ghait M, Husain RA, Duduskar SN, Haack TB, Rooney M, Gohrig B, Bauer M, Rubio I, Deshmukh SD (2022) The TLR-chaperone CNPY3 is a critical regulator of NLRP3-inflammasome activation. Eur J Immunol 52: 907-923 https://pubmed.ncbi.nlm.nih.gov/35334124/

Osuchowski MF, Winkler MS, Skirecki T, Cajander S, Shankar-Hari M, Lachmann G, Monneret G, Venet F, Bauer M, Brunkhorst FM, Weis S, Garcia-Salido A, Kox M, Cavaillon JM, Uhle F, Weigand MA, Flohe SB, Wiersinga WJ, Almansa R, de la Fuente A, Martin-Loeches I, Meisel C, Spinetti T, Schefold JC, Cilloniz C, Torres A, Giamarellos-Bourboulis EJ, Ferrer R, Girardis M, Cossarizza A, Netea MG, van der Poll T, Bermejo-Martin JF, Rubio I. The COVID-19 puzzle: deciphering pathophysiology and phenotypes of a new disease entity. Lancet Respir Med. 2021;9(6):622-642. https://pubmed.ncbi.nlm.nih.gov/33965003/

Rubio I, Osuchowski MF, Shankar-Hari M, Skirecki T, Winkler MS, Lachmann G, La Rosee P, Monneret G, Venet F, Bauer M, Brunkhorst FM, Kox M, Cavaillon JM, Uhle F, Weigand MA, Flohe SB, Wiersinga WJ, Martin-Fernandez M, Almansa R, Martin-Loeches I, Torres A, Giamarellos-Bourboulis EJ, Girardis M, Cossarizza A, Netea MG, van der Poll T, Scherag A, Meisel C, Schefold JC, Bermejo-Martin JF. Current gaps in sepsis immunology: new opportunities for translational research. Lancet Infect Dis. 2019;19(12):e422-e436. https://pubmed.ncbi.nlm.nih.gov/31630991/

Borken F, Markwart R, Requardt RP, Schubert K, Spacek M, Verner M, Ruckriem S, Scherag A, Oehmichen F, Brunkhorst FM, Rubio I. Chronic Critical Illness from Sepsis Is Associated with an Enhanced TCR Response. J Immunol. 2017;198(12):4781-91. https://pubmed.ncbi.nlm.nih.gov/28484052/

Publications 2024

De Biasi S, Lo Tartaro D, Neroni A, Rau M, Paschalidis N, Borella R, Santacroce E, Paolini A, Gibellini L, Ciobanu AL, Cuccorese M, Trenti T, Rubio I, Vitetta F, Cardi M, Argüello RJ, Ferraro D, Cossarizza A (2024) Immunosenescence and vaccine efficacy revealed by immunometabolic analysis of SARS-CoV-2-specific cells in multiple sclerosis patients. Nat Commun 15: 2752 https://pubmed.ncbi.nlm.nih.gov/38553477/

Eberhardt N, Santamarina BG, Enghardt ML, Rohland O, Hussain I, Tannert A, Thieme L, Rubio I, Rödel J, Löffler B, Arndt HD, Bauer M, Busch A (2024) The effects of photoactivated ciprofloxacin and bile acids on biofilms on bile duct catheters. Int J Antimicrob Agents 63: 107086 https://pubmed.ncbi.nlm.nih.gov/38218325/

Rooney M, Duduskar SN, Ghait M, Reißing J, Stengel S, Reuken PA, Quickert S, Zipprich A, Bauer M, Russo AJ, Rathinam VA, Stallmach A, Rubio I, Bruns T. Type-I interferon shapes peritoneal immunity in cirrhosis and drives caspase-5-mediated progranulin release upon infection. J Hepatol. 2024. DOI: 10.1016/j.jhep.2024.06.019 https://pubmed.ncbi.nlm.nih.gov/38936554/

Santacroce E, D'Angerio M, Ciobanu AL, Masini L, Lo Tartaro D, Coloretti I, Busani S, Rubio I, Meschiari M, Franceschini E, Mussini C, Girardis M, Gibellini L, Cossarizza A, De Biasi S (2024) Advances and Challenges in Sepsis Management: Modern Tools and Future Directions. Cells 13(5):439 https://pubmed.ncbi.nlm.nih.gov/38474403/

von Loeffelholz C, Winkler R, Weigel C, Piskor EM, Vivas W, Rauchfuß F, Settmacher U, Rubio I, Weis S, Gräler MH, Bauer M, Kosan C. Increased peritoneal B1-like cells during acute phase of human septic peritonitis. iScience. 2024;27(7):110133. DOI: 10.1016/j.isci.2024.110133 https://pubmed.ncbi.nlm.nih.gov/38984201/

Publications 2023

Garloff V, Krüger T, Brakhage A, Rubio I (2023) Control of TurboID-dependent biotinylation intensity in proximity ligation screens. J Proteomics 279: 104886 https://pubmed.ncbi.nlm.nih.gov/36966971/

Hussain I, Sureshkumar HK, Bauer M, Rubio I (2023) Starvation Protects Hepatocytes from Inflammatory Damage through Paradoxical mTORC1 Signaling. Cells 12: 1668 https://pubmed.ncbi.nlm.nih.gov/37371138/

Leonhardt J, Dorresteijn MJ, Neugebauer S, Mihaylov D, Kunze J, Rubio I, Hohberger FS, Leonhardt S, Kiehntopf M, Stahl K, Bode C, David S, Wagener F, Pickkers P, Bauer M (2023) Immunosuppressive effects of circulating bile acids in human endotoxemia and septic shock: patients with liver failure are at risk. Crit Care 27: 372 https://pubmed.ncbi.nlm.nih.gov/37759239/

Naumann M, Arend N, Guliev RR, Kretzer C, Rubio I, Werz O, Neugebauer U (2023) Label-Free Characterization of Macrophage Polarization Using Raman Spectroscopy. Int J Mol Sci 24: 824 https://pubmed.ncbi.nlm.nih.gov/36614272/

Osadare IE, Xiong L, Rubio I, Neugebauer U, Press AT, Ramoji A, Popp J (2023) Raman Spectroscopy Profiling of Splenic T-Cells in Sepsis and Endotoxemia in Mice. Int J Mol Sci 24: 12027 https://pubmed.ncbi.nlm.nih.gov/37569403/

Publications 2022

Publications 2021

Baker MJ, Rubio I (2021) Active GTPase Pulldown Protocol. Methods Mol Biol 2262: 117-135 Active GTPase Pulldown Protocol - PubMed (nih.gov)

Kulhanek KR, Roose JP, Rubio I (2021) Regulation of the Small GTPase Ras and Its Relevance to Human Disease. Methods Mol Biol 2262: 19-43 https://pubmed.ncbi.nlm.nih.gov/33977469/

Manzano S, Gutierrez-Uzquiza A, Bragado P, Sequera C, Herranz Ó, Rodrigo-Faus M, Jauregui P, Morgner S, Rubio I, Guerrero C, Porras A (2021) C3G downregulation induces the acquisition of a mesenchymal phenotype that enhances aggressiveness of glioblastoma cells. Cell Death Dis 12: 348 https://pubmed.ncbi.nlm.nih.gov/33824275/

Winkler MS, Skirecki T, Brunkhorst FM, Cajander S, Cavaillon JM, Ferrer R, Flohe SB, Garcia-Salido A, Giamarellos-Bourboulis EJ, Girardis M, Kox M, Lachmann G, Martin-Loeches I, Netea MG, Spinetti T, Schefold JC, Torres A, Uhle F, Venet F, Weis S, Scherag A, Rubio I, Osuchowski MF. Bridging animal and clinical research during SARS-CoV-2 pandemic: A new-old challenge. EBioMedicine. 2021;66:103291. https://pubmed.ncbi.nlm.nih.gov/33813139/

Corrections

Hussain I, Sureshkumar HK, Bauer M, Rubio I. Correction: Hussain et al. Starvation Protects Hepatocytes from Inflammatory Damage through Paradoxical mTORC1 Signaling. Cells 2023, 12, 1668. Cells. 2024;13(18). DOI: 10.3390/cells13181570 https://pubmed.ncbi.nlm.nih.gov/39329780/